rs9459502

Variant names:

• chr6-165760413-T-C
• rs9459502
• ENST00000647768.3:c.107-49260A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000647768.3(PDE10A):​c.107-49260A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 152,066 control chromosomes in the GnomAD database, including 39,115 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.71 (39115 hom., cov: 32)
• Consequence: PDE10A ENST00000647768.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209
• Publications: 2 publications found

Genes affected

PDE10A (HGNC:8772): (phosphodiesterase 10A) The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase family. It plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This protein can hydrolyze both cAMP and cGMP to the corresponding nucleoside 5' monophosphate, but has higher affinity for cAMP, and is more efficient with cAMP as substrate. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Dec 2011]

PDE10A Gene-Disease associations (from GenCC):

• striatal degeneration, autosomal dominant 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• dyskinesia, limb and orofacial, infantile-onset

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics
• infantile-onset generalized dyskinesia with orofacial involvement

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• childhood-onset benign chorea with striatal involvement

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000236627 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE10A	XM_011535387.4	c.59-49260A>G		intron_variant	Intron 2 of 23		XP_011533689.2
PDE10A	XM_017010194.3	c.59-49260A>G		intron_variant	Intron 2 of 23		XP_016865683.1
PDE10A	XM_017010197.3	c.59-49260A>G		intron_variant	Intron 2 of 18		XP_016865686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE10A	ENST00000647768.3	c.107-49260A>G		intron_variant	Intron 1 of 22			ENSP00000497930.3
PDE10A	ENST00000672902.1	c.-17-49260A>G		intron_variant	Intron 1 of 22			ENSP00000500351.1
PDE10A	ENST00000672859.1	c.-18+31498A>G		intron_variant	Intron 3 of 24			ENSP00000500900.1

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107515 AN: 151948 Hom.: 39098 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.794

Gnomad OTH AF: 0.763

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.707 AC: 107569 AN: 152066 Hom.: 39115 Cov.: 32 AF XY: 0.704 AC XY: 52335 AN XY: 74314

African (AFR) AF: 0.537 AC: 22268 AN: 41454

American (AMR) AF: 0.773 AC: 11829 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.855 AC: 2968 AN: 3470

East Asian (EAS) AF: 0.589 AC: 3040 AN: 5162

South Asian (SAS) AF: 0.752 AC: 3619 AN: 4810

European-Finnish (FIN) AF: 0.695 AC: 7337 AN: 10564

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.794 AC: 54022 AN: 68000

Other (OTH) AF: 0.755 AC: 1591 AN: 2106

Alfa AF: 0.764 Hom.: 25858

Bravo AF: 0.705

Asia WGS AF: 0.676 AC: 2351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.5
DANN	Benign	0.37
PhyloP100		-0.21

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9459502; hg19: chr6-166173901;